With erectile dysfunction (ED), there is an inability to develop and maintain an erection for sexual intercourse. The condition may result from psychogenetic or organic causes that alter the patient's erectile response. Variations in intensity make erectile dysfunction and its incidence in the population difficult to define. Depending on the definition used, there are varying estimates of from 15 to 30 million affected men in the world. According to the National Ambulatory Medical Care Survey (NAMCS), in 1985, of every 1000 men in the United States who visited their doctor, about eight discussed erectile dysfunction. In 1999, that number almost tripled (to about 22 men per thousand), perhaps because treatments were beginning to be released and discussion about erectile dysfunction began to be more accepted. The most publicised treatment has been the oral medication sildenafil citrate (Viagra®) (see, e.g., U.S. Pat. No. 6,204,383). NAMCS data indicates that Viagra® was mentioned about 2.6 million times during medical visits in 1999, and a third of those visits were for diagnostic reasons unrelated to ED.
The erection process requires a sequence of events and ED can occur when any of these is interrupted. The required events include nerve impulses in the brain, spinal cord, and area around the penis, and various responses in muscles, fibrous tissues, veins, and arteries in and near the corpus cavernosa. Erectile dysfunction is sometimes associated with a disease such as diabetes, kidney disease, chronic alcoholism, multiple sclerosis, arteriosclerosis, vascular disease or neurological disease, but it can also be a side effect of medication (e.g., a side effect of an antihypertensive, an antihistamine, antidepressant, tranquilizer, appetite suppressant, or cimetidine). Other causes include trauma, including surgery (in particular, prostate surgery) that results in nerve damage or restricts blood flow to the penis. In the absence of any organic cause, ED may be determined to be of psychological origin (PED), due to depression, anxiety, stress, tension, or guilt. ED is not a normal consequence of aging, but its incidence does increase with age. About 5% of 40-year-old men and between 15 and 25% of 65-year-old men experience ED. Successful treatment can occur at any age.
Standard drug treatments for ED include a class of drugs known as phosphodiesterase 5 (PDE-5) inhibitors (e.g., sildenafil citrate (Viagra®)). Although these drugs can be very effective, about 30% of all patients treated are refractile to their effects. The PDE5 inhibitors are associated with side effects including headache, flushing, upset stomach, stuffy nose, urinary tract infection, visual changes such as mild and temporary changes in blue/green colors or increased sensitivity to light, and diarrhea. Moreover, these drugs are contraindicated in patients who are taking nitrate drugs for angina, such as nitroglycerin (Nitro-Bid™ and others), isosorbide mononitrate (Imdur™) and isosorbide dinitrate (Isordil™); anticoagulants, and certain types of alpha blockers for enlarged prostate (benign prostatic hyperplasia) or high blood pressure. The PDE5 inhibitors may not be suitable for patients who have severe heart disease, heart failure, hypotension, hypertension, uncontrolled diabetes or who have had a stroke, or for those patients with haematological disorders that may be associated with priapism (e.g., anaemia of falciform cells, multiple myeloma or leukaemia). Accordingly, there is a continuing need for safe and effective therapies for treatment of ED.